Abstract

The evolutionary relationship and functional correlation between human formyl peptide receptors (FPRs) and their mouse counterparts remain incompletely understood. We examined 3 members of the mouse formyl peptide receptor subfamily (mFprs) and found that they differ in agonist preference and cellular distributions. When stably expressed in transfected RBL-2H3 cells, mFpr1 was readily activated by N-formylated peptides derived from Listeria monocytogenes (fMIVTLF), Staphylococcus aureus (fMIFL) and mitochondria (fMMYALF). In contrast, the Escherichia coli-derived fMLF was 1,000-fold less potent. The above peptides were much less efficacious at mFpr2, which responded better to the synthetic hexapeptide WKYMVm, the synthetic agonists Quin-C1 (a substituted quinazolinone), and Compound 43 (a nitrosylated pyrazolone derivative). Saturation binding assays showed that mFpr1 and mFpr2 were expressed at similar levels on the cell surface, although their affinity for fMLFIIK-FITC varied by more than 1,000-fold (Kd values of 2.8 nM for mFpr1 and 4.8 μM for mFpr2). Contrary to these receptors, mFpr-rs1 responded poorly to all peptides tested above. Fluorescent microscopy revealed an intracellular distribution pattern of mFpr-rs1. Based on these results, we conclude that mFpr1 is an orthologue of human FPR1 with certain pharmacological properties of human FPR2/ALX, whereas mFpr2 has much lower affinity for formyl peptides. The intracellular distribution of mFpr-rs1 suggests an evolutionary correlation with human FPR3.